Post-translational modifications (PTMs) is one of the major events causing the appearance of neo cryptic epitopes able to activate the immune system. Citrullination and carbamylation are well known examples of PTMs that generate targets of autoantibodies. Enzymatic modification of arginine in citrulline in histones is the prerequisite of NETosis, it is conceivable that other post translational modifications may occur during this event. PTMs of proteins may elicit an autoimmune response that leads to autoantibodies formation. Several autoimmune diseases seem to share these pathogenic mechanisms, in particular Anti-Phospholipid Syndrome (APS), an autoimmune entity defined by clinical and laboratory criteria, associated with thrombotic and/or obstetric morbidities. Some patients with clinical profile suggestive of APS are persistently negative for the routinely used antiphospholipid antibodies (aPL), these cases are known as "Seronegative APS" (SN-APS).
Since, dysregulation in PTMs of specific proteins represents triggers of processes potentially leading to autoimmunity, we will clarify how carbamylated- or acetylated-modified ß2GPI are able to activate the immune response and whether it may contain additional epitopes for anti-ß2GPI reactivity in those cases of SN-APS patients. We will explore whether these modified antigens are able to activate monocyte-derived immature DCs from healthy human donors.
Moreover, since both NETosis and extracellular microvesicles (MV) seem to be active in several autoimmune conditions, contributing to the formation of inflammation-induced thrombosis associated with autoimmune diseases, it will be interesting to characterize NET components and extracellular MV in the circulation of APS and SN-APS patients, correlating the new findings with clinical data and the presence of anti-Car-ß2GPI antibodies. This creates a link between innate immunity and autoimmunity that may explain autoantibodies formation.
